文章基本信息

标题：On the Origin of ATP Synthesis in Cancer
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作者：Thomas N. Seyfried ; Gabriel Arismendi-Morillo ; Purna Mukherjee 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：11
页码：1-21
DOI：10.1016/j.isci.2020.101761
语种：English
出版社：Elsevier
摘要：ATP is required for mammalian cells to remain viable and to perform genetically programmed functions. Maintenance of the ΔG′ATPhydrolysis of −56 kJ/mole is the endpoint of both genetic and metabolic processes required for life. Various anomalies in mitochondrial structure and function prevent maximal ATP synthesis through OxPhos in cancer cells. Little ATP synthesis would occur through glycolysis in cancer cells that express the dimeric form of pyruvate kinase M2. Mitochondrial substrate level phosphorylation (mSLP) in the glutamine-driven glutaminolysis pathway, substantiated by the succinate-CoA ligase reaction in the TCA cycle, can partially compensate for reduced ATP synthesis through both OxPhos and glycolysis. A protracted insufficiency of OxPhos coupled with elevated glycolysis and an auxiliary, fully operational mSLP, would cause a cell to enter its default state of unbridled proliferation with consequent dedifferentiation and apoptotic resistance, i.e., cancer. The simultaneous restriction of glucose and glutamine offers a therapeutic strategy for managing cancer.Graphical AbstractDisplay OmittedBiological Sciences; Biochemistry; Cell Biology; Cancer Systems Biology